With an established population of elderly subjects with strictly defined mild senile dementia/Alzheimer type (SDAT) and matched healthy elderly controls, we are continuing the longitudinal investigation of the interrelationships and predictive value of clinical, behavioral and multiple biomedical factors. Serial assessments include detailed clinical examinations, psychometric test battery, advanced quantitative CT, EEG, study of event-related potentials (ERP), positron emission tomography (PET), and assay of plasma levels of S-100 protein, a biochemical marker of impaired glial cell integrity. Having found significant differences between mild SDAT subjects and controls on some of these measures, we are starting a prospective study on elderly subjects with cognitive impairment too mild to be diagnosed as SDAT. These subjects and matched controls will be studied by the same measures given above, with the goal of identifying interrelationships and factors which predict the development of SDAT. At a single assessment we will study subjects with mild, moderate and severe SDAT by clinical, psychometric, CT, EEG, and ERP measures. We will compare results from a "cross-sectional" assessment with those of the longitudinal study. The PET study will describe local cerebral hemodynamics and metabolism in healthy aging and SDAT to explore PET's role in diagnosis and prognosis. Further, it may provide evidence for the role, if and, of brain circulation in pathogenesis of SDAT. We will assess all subjects serially with measures of behavior (activities of daily living, functional capacities) for comparison with our other studies. The longitudinal impact of SDAT on the primary caregiver will also be assessed. The possible relationship between susceptibility to SDAT and HLA antigen frequencies will be examined by HLA study of all subjects. Subjects will be followed until autopsy when results of pathologic examination of the brain will be compared with previous data. Remaining brain tissue will be frozen and stored. These studies have bearing on the enormous national health problem o senile dementia and on the important adaptive capabilities of the healthy elderly.